THE EFFECT OF N-METHYL-D-ASPARTATE ANTAGONIST (KETAMINE) ON SINGLE AND REPEATED NOCICEPTIVE STIMULI - A PLACEBO-CONTROLLED EXPERIMENTAL HUMAN STUDY

Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) receptor chan nel blocker known to inhibit ''wind-up'' and hence central hyperexcita bility of dorsal horn neurons. We sought to assess the effect of ketam ine on single and repeated nociceptive stimuli. A placebo-controlled, human (12 volunteers) experimental study was conducted in which severa l psychophysical (pain detection and tolerance thresholds, magnitude r atings) and electrophysiologic (withdrawal reflex) techniques were use d 1) to investigate whether a ketamine (0.5 mg/kg) bolus followed by a 20-min infusion (9 mu g . kg(-1) . min(-1)) inhibits central temporal summation to repeated nociceptive electrical stimuli, and 2) to asses s quantitatively the hypoalgesic potency using several experimental no ciceptive stimuli (argon laser, pressure, electrical). Facilitation of the withdrawal reflex to and pain rating of repeated electrical stimu li (five pulses at 2 Hz) were inhibited by ketamine. Reflex and pain r ating to a single stimulus did not change. The pressure pain detection and tolerance thresholds were increased significantly by ketamine, wh ereas the laser heat pain and tolerance thresholds remained stable com pared with placebo. The stimulus response function showed that ketamin e reduced the responses to the highest electrical stimulus intensities (1.4, 1.6, and 1.8 times the reflex threshold). We conclude that keta mine inhibits central temporal summation in humans and has a marked hy poalgesic effect on high intensity nociceptive stimuli.